Extracorporeal shock wave lithotripsy has become the primary treatment modality for urinary stones. Recently, a growing number of new lithotripters (second and third generation machines) have been developed. Yet, the fundamental mechanisms for stone fragmentation as well as the potential acute and long term deleterious effects on renal tissue and function have not been completely explained. The need remains for further basic shock wave physics and animal studies. We propose to continue our investigations to better understand the mechanics of stone-tissue-wave interactions, the mechanisms of stone fragmentation and of renal tissue injury, and to further characterize the effects of lithotripter energy sources, machine settings, and treatment strategies on clinical shock wave lithotripsy efficacy and safety. A series of experimental and theoretical studies have been designed and are grouped into four aims of this project: 1) mechanisms of tissue injury and limitation of damage during lithotripsy; 2) computer modeling of stone- tissue-shock wave interaction; 3) physical characterization of renal calculi and renal tissues; and 4) establishment of damage criteria for stone fragmentation and renal tissue injury. The overall goal of this project is to integrate information from a broad range of basic physical and animal studies to establish optimized treatment parameters, with maximally efficient stone comminution, minimal renal tissue damage and functional changes. Results from this project shall lay the foundation for the clinical investigations in Project 2 which are formulated to optimize treatment strategies for the management of renal nephrolithiasis with extracorporeal shock wave lithotripsy.